Lymphoma in an HIV-positive patient.

HIV/AIDS is considered to be revealing of oncological diseases, of which most frequent are lymphomas. The main causes for this type of disease are non-adherence and non-compliance to antiretroviral therapy (ART). We are hereby presenting a clinical case of lymphoma in an HIV-infected adult, with non-adherence for 30 months. In such a case the interdisciplinary collaboration with the hematologist was essential for the patient's survival.

Pact with the devil: alemtuzumab therapy, immune suppression and infectious complications in chronic lymphocytic leukemia.

Infectious complications are an important cause of hospitalization in patients diagnosed with chronic lymphocytic leukemia. The pathogenesis of infection is complex, involving both disease-induced and treatment-related immune depression. During the last decade, the management of chronic lymphocytic leukemia (CLL) has been redefined by the approval of monoclonal antibody-based treatment, which resulted in improved therapeutic responses. Nonetheless, the profound lymphopenia induced by monoclonal agents was accompanied by increased incidence of infections caused by a new spectrum of opportunistic microorganisms. We report the case of a patient with hypercellular CLL who received Alemtuzumab as first line therapy and obtained a satisfactory therapeutic response, but developed subsequent atypical infectious complications.

Leishmaniasis--an unusual cause of splenomegaly in Romania.

Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Romania is not considered an endemic country and there are only few reports of sporadic cases in the last 100 years. However, studies suggest that the disease is spreading north. We present the case of a 44 year old female that presented with asthenia, perspirations, vertigo, weight loss and menometrorhagias in small to medium quantity. Clinical exam revealed the presence of splenomegaly and her blood tests indicated she had pancitopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections that evolve with spleen enlargement, autoimmune-related splenomegaly and hepatic--all tests were negative. She refused the bone marrow aspiration. Three months later, her condition worsened and the menometrorragias became more severe. Bone marrow aspiration revealed the presence of numerous intra and extracellular Leishmania spp. amastigotes. A detailed anamnesis showed that she had worked for six months in Italy as a care-giver nine months ago. She was transferred to Bucharest where she received optimal treatment. However, due to the continuous bleeding, the evolution was unfavourable. This is an alarm sign for physicians that should take into account the fact that, due to population migration and global warming, tropical infectious diseases are becoming more and more common. The signs and symptoms, as well as the treatment in leishmaniasis are reviewed, as well as a brief history of leishmaniasis in Romania.

[Prognostic significance of leukemia-associated phenotype in correlation with other biologic markers in acute myeloid leukemia patients]. / Identificarea semnificatiei prognostice a fenotipului asociat leucemiei in corelatie cu alti markeri biologici la pacientii cu leucemie acuta mieloblastica.

UNLABELLED: Leukemic cells have unique aberrant phenotypes, which permit identification of this cells at diagnose and in evolution of the disease. Signaling molecules with other cells and bone marrow stroma are part of the leukemic cells phenotype. Genetic and molecular abnormalities have the main prognostic significance and confer the leukemic cell status. The main aim of the current study is to identify correlation between recognized prognostic factors in acute myeloid leukemia (AML) patients and other phenotypic markers. MATERIAL AND METHOD: Imunophenotypic analysis (BDFACS CantoII, FACSDiva Software) was performed on peripheral blood/bone marrow aspirate samples of 56 patients diagnosed with AML (9 M0, 3 M1, 10 M2, 4 M3, 28 M4/M5, 1 M6, 1 M7) between 2007-2009 in Hematology Department of "Sf. Spiridon" Hospital Iasi. We used an extended panel of monoclonal antibodies and we determined the level of expression of cytokines receptors (IL3Ra, IL7R) and chemokines (CXCR4, CKR5). RESULTS: In our study, IL7R expression on AML blasts was significant correlate with low WBC count at diagnosis (p = 0.04) and with multilinear displasia (p = 0.01), high CXCR4 expression was correlate (p = 0.05) with lack of response at first induction therapy and CD123 (IL3Ra) expression was correlate with M4 FAB phenotype. Survival was negative influenced by presence of IL3R on AML blasts, but flt3 mutations, CXCR4, IL7R expression on leukemic cells, other phenotypic aberrancies did not influenced treatment response and survival in our patients population. CONCLUSION: Complete investigation of leukemic cells phenotype extended with cytokines/chemokines receptors at diagnostic is useful for correct characterization of the disease, for discover new prognostic categories and for better identification of minimal residual disease.

Flow cytometry-based quantification of cytokine levels in AML patients plasma and cell culture supernatants.

AIM: Bone marrow stromal cells (BMSCs) have been found to support leukemic cell survival; however, the mechanisms responsible are far from being elucidated yet. The main aim of the current study is to identify particular cytokine/chemokine patterns of acute myeloid leukemia (AML) cells, and, on a longer term, to correlate them with the patient outcome and response to therapy. Therefore, the influence of BMSCs on in vitro modulation of cytokine secretion (IL-1beta, TNF-alpha, IL-10, IFN-gamma, IL-4, IL-5, and IL-2) by AML cells as well as the AML cells supportive capacity of BMSCs-derived soluble factors was investigated. MATERIAL AND METHODS: With this purpose, we used an in vitro experimental model consisting in the evaluation of the effect of BMSC confluent layers-conditioning medium (BMSC-CM) on M4/5 AML cell cultures. RESULTS: Our results show that BMSC-CM from both AML patients and healthy subjects conferred a substantial beneficial effect on AML cells throughout the culture (p=0.0002 and 0.0020 respectively at 24 hours and p=0,0013 and 0,0030 respectively at 72 hours), with a temporary increase in AML cell viability conferred by BM plasma from AML patients. Significant differences were observed with respect to IL1 b secretion which was upregulated in AML cell cultures both after 24 and 72 hours following the addition of AML-BMSC-CM, in contrast to control-BMSC-CM. CONCLUSION: Our results suggest the contribution of BMSCs from AML patients to the generation of particular factors which may be key players involved in the in vivo maintenance of the malignant clone.

Influence of cigarette smoking on the presentation and course of acute myeloid leukemia.

BACKGROUND: It is known that cigarette smoking is associated with an approximately 50% increase in leukemia risk. In order to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of the disease, we conducted a retrospective study in 643 patients with newly diagnosed acute myeloid leukemia. PATIENTS AND METHODS: The study comprised 339 males and 304 females (median age 59 years, range 18-84 years). Two hundred and ninety-six patients (46%), smoking at least one cigarette per day for 6 months, were considered as smokers, while 347 patients (54%) were non-smokers. RESULTS: Cigarette smoking was significantly related to male gender (P <0.0001), professional occupancy (P = 0.002), presence of organomegaly (P = 0.01), and lower peripheral blood and bone marrow leukemic cell involvement (P = 0.007 and P = 0.0001, respectively). Leukemia of French-American-British (FAB) M1 subtype was more frequent in non-smokers (P = 0.005). Although not statistically significant, smokers tended to have lower leukocyte counts than non-smokers. No difference was noted in terms of complete remission rates between smokers and non-smokers (67% compared to 64%). However, a higher rate of severe pulmonary infection was observed in smokers during induction chemotherapy (P = 0.02). Cigarette smoking (>or=20 pack-years or smoking duration >or=30 years) was significantly associated with shorter disease-free survival (P = 0.03) and overall survival (OS; P = 0.02 and P = 0.004, respectively). Other characteristics associated with poor prognosis included mainly older age, unfavorable karyotype, secondary acute myeloid leukemia (AML) and elevated World Health Organization (WHO) performance status. Cigarette smoking was associated with shorter OS in younger adults, but did not significantly influence survival in patients >60 years old. Cigarette smoking worsened the poor OS in patients with unfavorable karyotype, but did not significantly influence the prognosis of other karyotypic risk groups. In a multivariate analysis, only karyotypic grouping and age remained of prognostic value for the occurrence of disease-free and overall survival. CONCLUSIONS: Cigarette smoking has a deleterious effect on survival in AML by shortening complete remission duration and subsequent survival. It was associated with severe infections during aplasia. Leukemogenic compounds favoring complex karyotypic abnormalities could also be involved.

[Thyroid cancer and chronic granulocytic leukemia in the same patient: Cernobyl or coincidence?]. / Cancer tiroidian si leucemie granulocitara cronica la acelasi pacient: cernobâl sau coincidenta?

We present a case of thyroidian cancer and chronic granulocytic leukemia simultaneously found in a 28 years old patient. Initial surgical management consisted in total thyroidectomy and removal of the lymph nodes; local recurrence after 6 months required excision of the tumoral block by radical neck dissection. Hematological disease was controlled with Hydroxiureea, associated, when needed, with Busulphan and Cytosar. The patient is in acceptable general condition and free of any local recurrence or apparent metastases 2.5 years after the diagnosis.

Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period.

Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.

[Castleman's disease. Discussion related to case report]. / Boala Castleman. Discutii în relatie cu un caz clinic.

Castleman's disease, also called angiofollicular hyperplasia was first described as a distinct entity by Castleman et al in 1956. Now there are described two forms, a localised and a multicentric one. All forms of disease share the same histopathological features with a highly characteristic angiofollicular lymphoid hyperplasia which is either hyalinovascular or plasmocytic. The clinical and biological signs are varied and heterogeneous. The disorder is of unknown origin, but interleukin 6 plays a central part in this disease. Despite the benignity of this "prelymphoma state", an aggressive course with poor prognosis occur usually in the multicentric form. We report a case of Castleman's disease, multicentric variant. This case provides the opportunity for discussing many aspects of this atypical lymphoproliferative disorder.

Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome.

Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is an aggressive form of acute leukemia that represents about one third of all adult ALL. Between 1984 and 1996, forty-three cases of Ph+ ALL (22 males and 21 females) were diagnosed in our institution by successful cytogenetic studies and/or molecular biology. Median age was 42 years (range, 20-71 years) with 28 patients aged below 50 years. Median leukocyte count was 39.7 x 10(9)/l on admission. Tumoral syndrome was seen only in 21 patients (49%) of which 4 cases presented with central nervous system (CNS) involvement. Among the 38 patients classified according to the French-American-British (FAB) criteria, 26 showed L1 and 9 L2 morphology. Three patients showed undifferentiated leukemia. Immunological study at diagnosis only showed B-cell lineage ALL with 95% of patients expressing CD10 and 50% expressing CD20. The Ph+ as sole anomaly was seen in 13 patients (31%), while additional chromosome changes were observed in 28 cases. Two patients were diagnosed only on molecular biology showing a Bcr/Abl rearrangement. Thirty-nine patients treated according to LALA protocols were eligible for the analysis of treatment outcome. Complete remission (CR) was achieved in 25 cases (64%, 95% CI: 47-79%). The median disease-free survival (DFS) and the median overall survival were 6 and 9 months respectively. Relapse was observed in 16 cases (64% of patients achieving CR). Initial parameters associated with a statistically significant worse prognosis were "blastic" fever, hyperuricemia, the presence of an extra Ph chromosome and patients whose marrow does not contain any normal mitosis (AA cases). As post-induction therapy, 13 cases followed a chemotherapy program (group 1) while 11 received early bone marrow (BM) or peripheral stem cell (PSC) transplantation (group 2) (5 allogeneic BM transplantation and 6 autologous BM or PSC transplantation). One patient did not receive any post-induction therapy. In group 1, the median DFS and overall survival were of 5 and 11 months respectively, while they were of 9 months and not reached respectively in group 2 with a 2-year survival rate of 51% (95% CI: 21-83%) confirming the requirement for intensified therapy in Ph+ ALL.

[Treatment of acute lymphoid leukemia in adults]. / Traitement des leucémies aiguës lymphoïdes de l'adulte.

Treatment of adult acute lymphoblastic leukemia (ALL) consists of two parts: induction of complete remission (CR) using a triple chemotherapy with prednisone, vincristine and one anthracycline associated in the majority of protocols with either asparaginase or cyclophosphamide or cytosine arabinoside. A CR rate of 75% can be obtained. The second part is the treatment during remission with 3 phases: early intensification or consolidation by chemotherapy, prevention of leukemia in the central nervous system and maintenance. Alternative strategies are allogeneic or autologous transplantation after myeloablative therapy. Overall long term survival is between 25 and 40%, for less than in children. Future direction of treatment are: better definition of heterogeneous forms of the disease with standard or high risk of relapse allowing adjustment of the treatment. Karyotype analysis, and molecular biology are mandatory to define high risk ALL such as Ph1 + ALL and also to know the level of residual disease during remission. For treatment strategy efficacy of transplantation must be improved (less toxicity for allogeneic BMT, less relapse for autologous BMT and more efficient chemotherapy regimen).

Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone in adult acute lymphoblastic leukemia.

Sequential chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone doses was administered to 57 adult patients with acute lymphoblastic leukemia (ALL). Complete remission (CR) was achieved in 51 (89%, 95% confidence intervals, [CI] 78-96%). Among patients achieving CR, 62% were in CR after one sequence of chemotherapy, 23% after two sequences, and 5% after three sequences. Six patients (11%) had resistant disease. All patients experienced profound myelosuppression. Median time to recovery of neutrophils > 0.5 x 10(9)/1 was 22 days (range: 5-89 days), and of platelets > 100 x 10(9)/1 21 days (range: 0-45 days). Nonhematologic WHO grade 3 or more side effects consisted predominantly of hyperbilirubinemia (7%), mucositis (5%), nausea and vomiting (2%), and cutaneous toxicity (1%). Severe infectious complications occurred in only 14% of cases. One patient (2%, 95% CI 0-9%) died of therapy-related toxicity while in early CR. We concluded that sequential use of prednisone seemed at least as effective as continuous administration at the expense of a few adverse side effects.